The objectives of research proposed in this request are continuations of those pursued in this laboratory over the past several years. (1) To define insofar as possible the biochemical and enzymatic profile of human blood cells. (2) To expand the available procedures for evaluating the metabolism of blood cells. (3) To define alterations in blood cell metabolism induced by acquired disease, by mutant enzymes, by genetically induced deficiency states, and by environmental factors such as diet and medication. (4) To exploit genetically determined "experiments of nature" in regard to obtaining more information about normal metabolism and its regulation, about human genetics, and in regard to possible modalities of therapy. Established technology in the laboratory currently permits assay of glycolytic enzymes, hexosemonophosphate shunt enzymes, certain enzymes of glutathione and nucleotide metabolism, and a number of other enzyme activities and metabolic intermediates.